Presentation on theme: "New Psychiatric Medications"— Presentation transcript:
1New Psychiatric Medications Knowledge is PowerGregory T. Bogart, Pharm.D., BCPPClinical Psychiatric PharmacistUniversity of Maryland, School of PharmacySpringfield Hospital CenterSykesville, MDJennifer Miller, Pharm.D., BCPPWilkes-Barre VAMCWilkes-Barre, PA
2ObjectivesDiscuss clinical indications of new and emerging psychiatric medicationsCompare and contrast the role of new medications with existing medicationsImplement strategies to learn about new psychiatric medications
7Iloperidone FDA approved in 2009 Indicated for the treatment of schizophrenia in adultsMechanism of action – primarily dopamine (D2) antagonism with some serotonin (5HT2) antagonismFanapt® [package insert]. East Hanover, NJ;Novartis Pharmaceuticals Corporation; Revised April, 2014.
8Iloperidone - Efficacy 6-week trial with placebo and risperidone showed superiority over placebo and comparable efficacy of risperidone at 6 weeks4-week trial with placebo and ziprasidone found superiority over placebo and similar efficacy to ziprasidone at 4 weeksFanapt® [package insert]. East Hanover, NJ;Novartis Pharmaceuticals Corporation; Revised April, 2014.
9Iloperidone – Possible Side Effects Metabolic changes – weight gain, ↑cholesterolNot as significant as other 2nd gen drugsExtrapyramidal symptoms (EPS)QTc prolongationOrthostasis, low blood pressure, and dizzinessRarer side effects – priapism, seizure, agranulocytosis
10Iloperidone - Dosing Starting dose 1 mg twice daily Target dosage range 6-12 mg twice dailyIncrease by no more than 2 mg twice daily every day until target rangeSlow titration due to increased risk of low blood pressure, dizziness, and fallsMaximum dose of 12 mg twice dailyFanapt® [package insert]. East Hanover, NJ;Novartis Pharmaceuticals Corporation; Revised April, 2014.
11Iloperidone – Role in therapy New second generation antipsychotic choiceLower risk for EPS and weight gain than other optionsHigher risk of orthostasis, dizziness, and falls especially during the initial titration phaseSlow titration phase and twice daily dosing may be difficult for some patients to work with
12Asenapine FDA approved in 2009 Indications Treatment of schizophrenia in adultsAcute treatment, either as monotherapy or adjunctive, or manic or mixed episodes of bipolar I disorder in adultsMechanism of action thought to be a combination of dopamine D2 and serotonin 5HT2 receptor blockadeSaphris® [package insert]. Whitehouse Station, NJ;Merck & Co., Inc.; Revised March, 2013.
13Asenapine – Efficacy in Schizophrenia Short term studiesA 6-week trial comparing asenapine to placebo showed superior efficacy asenapine at 6 weeksA 6-week trial comparing asenapine to placebo and haloperidol showed asenapine to be superior to placebo, but not haloperidol. It also showed no difference between 5 mg twice daily and 10 mg twice daily dosingA 6-weeks trial comparing asenapine to placebo olanzapine showed that asenapine and placebo failed to separate and that olanzapine was superior to bothSaphris® [package insert]. Whitehouse Station, NJ;Merck & Co., Inc.; Revised March, 2013.
14Asenapine – Efficacy in Bipolar I Disorder MonotherapyTwo 3-week trials of asenapine and placebo showed that asenapine was superior to placebo for controlling acute maniaAdjunctiveA 12-week trial of asenapine or placebo added to lithium or valproic acid showed asenapine was superior to placebo at reducing manic symptoms at 3 weeksSaphris® [package insert]. Whitehouse Station, NJ;Merck & Co., Inc.; Revised March, 2013.
15Asenapine – Possible Side Effects Metabolic changes and weight gainNot as significant as other 2nd gen drugsEPS – higher rates of akathisiaQTc prolongationSedation or somnolenceHeadacheRarer side effects – agranulocytosis, seizures, and orthostasisSaphris® [package insert]. Whitehouse Station, NJ;Merck & Co., Inc.; Revised March, 2013.
16Asenapine - Dosing Asenapine is supplied as sublingual tablets Do not swallow tabletsDissolve under the tongueNo food or drink for 10 minutes after doseIndicationStarting DoseDosage RangeMaximumSchizophrenia5 mg twice daily5-10 mg twice daily10 mg twice dailyAcute Bipolar ISaphris® [package insert]. Whitehouse Station, NJ;Merck & Co., Inc.; Revised March, 2013.
17Asenapine – Role in Therapy Can be utilized in both schizophrenia and bipolar disorderUnique sublingual administrationRelatively small metabolic side effectsHigher rates of sedation and akathisia than other agents
18Lurasidone FDA approved in 2010 Indications Treatment of schizophrenia in adultsTreatment of depressive episodes in bipolar disorder in adults as both monotherapy and adjunctive therapyMechanism of action thought to be a combination of dopamine D2 and serotonin 5HT2 receptor blockadeLatuda® [package insert]. Marlborough, MA;Sunovion Pharmaceuticals, Inc.; Revised July, 2013.
19Lurasidone – Efficacy in Schizophrenia Five total trials, all 6 weeks longTwo trials of fixed dose lurasidone vs. placebo showed superior efficacy of lurasidoneOne trial of 40 mg, 80 mg, and 120 mg lurasidone vs. placebo showed that only the 80 mg dose was superior to placeboOne trial of lurasidone, olanzapine and placebo showed that both lurasidone and olanzapine were superior to placeboOne trial of lurasidone, quetiapine ER, and placebo showed both lurasidone and quetiapine ER were superior to placeboLatuda® [package insert]. Marlborough, MA;Sunovion Pharmaceuticals, Inc.; Revised July, 2013.
20Lurasidone – Efficacy in Bipolar Depression As monotherapyA 6-week trial vs placebo for symptom reduction in bipolar depression showed that both doses of lurasidone studied were superior to placebo at 6 weeksAs an adjunctA 6-week trial of patients who were still symptomatic on lithium or valproic acid were given placebo or lurasidone. At 6 weeks, there was a superior symptom reduction in the lurasidone group vs. the placebo groupLatuda® [package insert]. Marlborough, MA;Sunovion Pharmaceuticals, Inc.; Revised July, 2013.
21Lurasidone – Possible Side Effects Metabolic changes and weight gainPossibly the most weight and metabolic neutralEPS – akathisia more common than othersQTc prolongationSedation or somnolenceNausea and vomitingRarer side effects – agranulocytosis, seizures, and orthostasisLatuda® [package insert]. Marlborough, MA;Sunovion Pharmaceuticals, Inc.; Revised July, 2013.
22Lurasidone - DosingFor schizophrenia, starting dose is 40 mg/day with a range of mg/dayFor bipolar depression, starting dose is 20 mg/day with a range of mg/dayAll doses should be taken with a meal of at least 350 calories to improve absorptionDosing is recommended in the evening due to the possibility of sedation and somnolenceLatuda® [package insert]. Marlborough, MA;Sunovion Pharmaceuticals, Inc.; Revised July, 2013.
23Lurasidone – Role in Therapy Can be utilized in schizophrenia and bipolar depressionHas a very favorable long-term metabolic profileOnce daily dosing is most patient friendlyAppears to be the most rigorously studied of the newer agents
25Rationale LAIs are options to improve compliance Less frequent administration than oral agentsDoses converted from stable oral regimensGuaranteed drug level in the body post-injectionImproved clinician contact
27Zyprexa Relprevv® FDA approved in 2009 Long acting intramuscular injection of olanzapine intended for gluteal injection onlyIndicated for the treatment of schizophreniaDesigned to be initiated after a stable regimen of olanzapine is establishedZyprexa Relprevv® [package insert]. Indianapolis, IN;Eli Lilly and Company; Revised July, 2011.
28Zyprexa Relprevv® - Dosing Oral dose of olanzapineDose of Zyprexa Relprevv® for the first 8 weeksMaintenance dose of Zyprexa Relprevv®after 8 weeks10 mg/day210 mg every 2 weeks or405 mg every 4 weeks150 mg every 2 weeks or300 mg every 4 weeks15 mg/day300 mg every 2 weeks20 mg/dayNote: No oral medication overlap is requiredZyprexa Relprevv® [package insert]. Indianapolis, IN;Eli Lilly and Company; Revised July, 2011.
29Adverse Events Adverse events are similar to oral olanzapine Metabolic syndrome and weight gainSedationOrthostasis and dizzinessAlso has Post-Injection Delirium/Sedation Syndrome (PDSS) riskZyprexa Relprevv® [package insert]. Indianapolis, IN;Eli Lilly and Company; Revised July, 2011.
30PDSS Signs and symptoms associated with olanzapine overdose Sedation and/or delirium possibly leading to comaDizziness, confusion, disorientation, slurred speech, weakness, difficulty walkingOccurred in <0.1% of all injections, 2% of all patients treated in 46 monthsMost patients recovered with supportive care within 72 hoursLead to the creation of a REMS programZyprexa Relprevv® [package insert]. Indianapolis, IN;Eli Lilly and Company; Revised July, 2011.
31Zyprexa Relprevv® REMS Prescriber, patient, facility, and pharmacy must all registerMedication cannot be dispensed directly to patientMedication must be administered in a registered facility with access to emergency response servicesPatients must be observed by a healthcare worker for at least 3 hours after injection for signs of PDSSPatients may not leave the facility by themselvesPatients should not drive the remainder of the dayZyprexa Relprevv® [package insert]. Indianapolis, IN;Eli Lilly and Company; Revised July, 2011.
32Abilify Maintena® FDA approved in 2013 Long acting intramuscular injection of aripiprazole intended for gluteal injection onlyIndicated for the treatment of schizophreniaDesigned to be initiated after a stable regimen of aripiprazole is establishedAbilify Maintena® [package insert]. Tokyo, Japan;Otsuka Pharmaceutical Co. Ltd; Revised February, 2013.
33Abilify Maintena® Dosing Recommended starting dose in 400 mg monthlyContinuation of oral aripiprazole mg/day is necessary for 14 days after initial injectionMaintenance dose is also 400 mg monthlyDose reduction to 300 mg can be used if 400 mg dose is intolerableAbilify Maintena® [package insert]. Tokyo, Japan;Otsuka Pharmaceutical Co. Ltd; Revised February, 2013.
34Adverse Events Very similar to oral aripiprazole Slight metabolic changesSome EPS – mostly akathisiaAnxietyHeadacheOrthostasisAbilify Maintena® [package insert]. Tokyo, Japan;Otsuka Pharmaceutical Co. Ltd; Revised February, 2013.
39Viibryd® (Vilazodone) Year Approved2011IndicationMajor Depressive DisorderViibryd ® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;Revised December, 2012.Image from
40Viibryd® (Vilazodone) Mechanism of ActionSelective Serotonin Reuptake Inhibitor (SSRI)Activity at serotonin receptorEffectivenessDecreased depressive symptoms in 8 week trials better than placeboPartial 5HT-1A agonistDecreased depressive symptoms in two 8 week RCT trials of outpatientsViibryd ® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;Revised December, 2012.
41Viibryd® (Vilazodone) SafetyContraindicationsUse with MAOIWarningsSerotonin syndrome, suicidality, seizure, mania, bleed, low sodium, sudden discontinuationSuicidality – In children, teenagers & young adults <= 24 y/o. Monitored for change in mood, thoughts, behaviors, actions or feelings and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during initial few months and dose changes. Daily observation by family & caregivers.SS – GI upset, agitation, hallucinations, delirium, and coma, autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrheaSeizure – not studiedHyponatremia & bleed – no cases but with other SSRIs – headache, weakness, confusionViibryd ® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;Revised December, 2012.
42Viibryd® (Vilazodone) SafetyDrug interactionsAdverse EffectsNausea, diarrhea, dizziness, sleep disturbance, sexual dysfunctionDI - 3A4 substrate, NSAIDs, Serotonergic meds/MAOIsTransient vs chronicViibryd ® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;Revised December, 2012.
43Viibryd® (Vilazodone) Considerations for UseTake with foodDose titrationNo dose adjustment for agePregnancy, nursing, or childrenMedication RoleNo clear advantage over SSRIs for depressionW/ food – or decrease  by 50%Titration - 10 mg once daily for 7 days, followed by 20 mg once daily for an additional 7 days, and then an increase to 40 mg once dailyNo human data in preg, lactation or childrenViibryd ® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;Revised December, 2012.
44Fetzima® (Levomilnacipran) Year Approved2013IndicationMajor Depressive DisorderMore active enantiomer of milnaciprin (approved in 2009 for fibromyalgia)More selective for NE - Tx norepinephrine deficiency symptoms - decreased concentration, lassitude, mental and physical slowing, and decreased self-care.3,4 Some authors claim that individual patients could experience improvement in their social and occupational functioning in addition to improvement in the core symptoms of depression.5Fetzima® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;Revised July, 2013.Image from
45Fetzima® (Levomilnacipran) Mechanism of ActionSerotonin Norepinephrine Reuptake Inhibitor (SNRI)EffectivenessDecreased depressive symptoms in 8 week trials better than placeboDecreased depressive symptoms in three 8 week RCT trials of outpatients (40-120mg all doses superior)Fetzima® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;Revised July, 2013.
46Fetzima® (Levomilnacipran) SafetyContraindicationsAllergic reaction, uncontrolled narrow-angle glaucoma, use with MAOIWarningsSerotonin syndrome, suicidality, seizure, mania, bleed, low sodium, sudden discontinuationWarnings not based on evidence directly from levomilnacipranFetzima® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;Revised July, 2013.
47Fetzima® (Levomilnacipran) SafetyWarnings (cont.)High blood pressure & heart rate, narrow-angle glaucoma, urinary hesitation or retentionDrug interactionsAdverse EffectsNausea, vomiting, constipation, sweating, increased blood pressure & heart rate, sexual dysfunctionThese warnings are based off data with levomilnacipranStrong 3A4 inhibitors like ketoconazole; avoid doses > 80mg/day; other medications which can increase BP & HRNo dose adjustment needed for 3A4 inducers(Other: serotonergic/MAOIs, drugs increasing BP & HR, drugs affecting homeostasis – NSAIDs)Alcohol accelerated drug release from ER capsulesUrinary hestitation & erectile dysfunction were dose relatedAlthough BP avg increase was only 3mmHg and HR was 7 bpm…trials excluded patients with significant CVDFetzima® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;Revised July, 2013.
48Fetzima® (Levomilnacipran) Considerations for UseAdjust dose for kidney impairmentNo dose adjustment for agePregnancy, nursing, childrenMedication RoleNo clear advantage over SNRIs for depressionNo established effectiveness for fibromyalgia/ painPregnancy – decreased birth weight and possibly mortality in rats at supratherapeutic doses.Nursing – present in rat milkChildren – no dataOnce daily dosing; ER tablet – do not split, etcBoth in-vitro and in-vivo studies found that levomilnacipran exhibited more potency for NE reuptake inhibition than for 5-HT reuptake inhibition at the lowest effective dosage (10 mg/kg). However as the dosage was increased (20 mg/kg and 40 mg/kg), it was equally potent at NE and 5-HT reuptake inhibition. This is in contrast to venlafaxine, which demonstrates a similar, but opposite, effect in terms of potentiation at the 5-HT and NE reuptake pumps.2NNT 6; NNT VNL was 8Fetzima® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;Revised July, 2013.
49Brintellix® (Vortioxetine) Year Approved2013IndicationMajor Depressive DisorderBrintellix® [package insert]. Deerfield, IL; Takeda PharmaceuticalsAmerica, Inc.; Revised July, 2014.Image from us.brintellix.com
50Brintellix® (Vortioxetine) Mechanism of ActionSSRIActivity at various serotonin receptorsEffectivenessDecreased depressive symptoms in 6-8 week trials & longer time to recurrent depression in 64 week trial better than placebo5HT3, 1D, 7 antagonism, 1A agonism, 1B partial agonist5mg not effective in 6-8 week trials; took 2 weeks for initial effect and about 4 weeks for full effectShort term studies with outpts and were RCTs; Longterm study was open label with inpts and outptsBrintellix® [package insert]. Deerfield, IL; Takeda PharmaceuticalsAmerica, Inc.; Revised July, 2014.
52Brintellix® (Vortioxetine) SafetyDrug interactionsAdverse EffectsNausea, vomiting, constipation, dizziness, sexual dysfunctionThe maximum recommended dose of BRINTELLIX is 10 mg/day in known CYP2D6 poormetabolizers. Reduce the dose of BRINTELLIX by one half when patients are receiving aCYP2D6 strong inhibitor (e.g., bupropion, fluoxetine, paroxetine, or quinidine) concomitantly.Consider increasing the dose of BRINTELLIX when a strong CYP inducer (e.g., rifampin,carbamazepine, or phenytoin) is coadministered for greater than 14 days. The maximumrecommended dose should not exceed three times the original dose.Nausea was dose related and resolved after ~ 2 weeksNo changes in weight or vital signs observed in pre-marketing trialsBrintellix® [package insert]. Deerfield, IL; Takeda PharmaceuticalsAmerica, Inc.; Revised July, 2014.
53Brintellix® (Vortioxetine) Considerations for UseAvoid in severe liver impairmentNo dose adjustment for agePregnancy, nursing, childrenMedication RoleNo clear advantage over SSRIs for depression-10 mg administered orally once daily without regard tomeals. Dosage should then be increased to 20 mg/day, as tolerated, because higher dosesdemonstrated better treatment effects in trials conducted in the United States. The efficacy andsafety of doses above 20 mg/day have not been evaluated in controlled clinical trials. A dosedecrease down to 5 mg/day may be considered for patients who do not tolerate higher doses-Although BRINTELLIX can be abruptly discontinued, in placebo-controlled trials patientsexperienced transient adverse reactions such as headache and muscle tension followingabrupt discontinuation of BRINTELLIX 15 mg/day or 20 mg/day. To avoid these adversereactions, it is recommended that the dose be decreased to 10 mg/day for one week before fulldiscontinuation of BRINTELLIX 15 mg/day or 20 mg/dayDevelopmental delays in rats; no adequate human trials; present in rat milk; no studies in peds; no dose adj needed for geri (like other 2 ad’s)No dose adj for geri, race, ethnicity, (like other ad’s) up to severe renal dys, but unknown with severe hepatic diseaseBrintellix® [package insert]. Deerfield, IL; Takeda PharmaceuticalsAmerica, Inc.; Revised July, 2014.
57Resources NAMI.org FDA.gov Drugs.com MedlinePlus Narsad.org Medication fact sheetsFDA.govDrugs.comMedlinePlusNarsad.orgSeek info on the internet; talk with health care providers!NAMI – inform yourself at bottom left – about medications at bottom leftFDA- a lot of links, but search function works wellThe site features FDA Consumer Update articles, videos, and slideshows. Site users can get valuable access to information about new drug approvals, use a drug interaction checker to check the compatibility of using two drugs at the same time, identify drugs from their tablet and capsule markings, ask questions to other site users, join support groups, and much more. Site users can also subscribe to the Drugs.com electronic newsletter and also sign up to receive alerts from FDA's MedWatch. MedlinePlus also offers a wide range of information about prescription drugs and dietary supplements. Additionally, this site provides information about many medical conditions and health issues treated with prescription medications. The site also provides a medical encyclopedia, a medical dictionary, an aid to find local health-related resources, and current health news and press announcements. The site can be used on over 40 languages. Narsad.org – “ask an expert”; blurbs about research and can search by mental illnessNational Alliance for Research on Schizophrenia and Depression – the Brain and Behavior Research Foundation